Odds ratio of 1.35; less risk than for certain other adverse outcomes

Action Points

Note that this observational study found that mothers with lupus were more likely to have children with allergies than mothers without lupus.

While it is likely that immune dysregulation is the common link here, it is unclear if the effect is mediated by genetics, antibodies, or other in utero exposures.

Children of mothers with systemic lupus erythematosus (SLE), a disorder of immune dysregulation, appear to be at somewhat increased risk of allergic conditions, a large case-control study in Arthritis Care & Researchindicated.

It found an odds ratio of 1.35 (95% CI 1.13-1.61) for allergies in offspring born to SLE mothers compared with control children. The effect was independent of obstetrical complications or maternal allergy history.

"Genetics, shared environmental exposures, as well as in utero exposure to maternal autoantibodies and cytokines may mediate this increased risk," wrote a Canadian team led by Julie Couture, MD, then of the McGill University Health Centre in Montreal, now of the Hospital for Sick Children in Toronto. They noted that only a few small, observational studies have assessed the risk of allergic conditions in the children of women with SLE.

Obstetrically, SLE affected mothers had about three times the rate of preterm birth (21.8% versus 7.5%) and more than twice the rate of small-for-gestational-age babies (16.7% versus 8.2%).

Children's subsequent allergic conditions (including asthma, allergic rhinitis, eczema, urticaria, angioedema, and anaphylaxis) were identified based on at least one hospitalization or one or two physician visits with a relevant diagnostic code.

After adjustment for maternal age, education, race/ethnicity, obstetrical complications, calendar year of birth, child's sex, and maternal medications, more children born to mothers with SLE had evidence of allergic conditions: 43.9% (95% CI 40.4%-47.6%) versus 38.1% (95% CI 37.0%-39.1%). Eczema, for example, was found in 16.4% of SLE mothers' children versus 12.7% of controls' offspring. The asthma rate was 16.1% versus 13.2%, while anaphylaxis came in at 0.8% versus 0.3%.

Using data from Quebec's large Offspring of SLE Mothers Registry, Couture and colleagues studied 719 children born live to 509 SLE mothers and matched them with 8,493 children born to 5,824 controls. The mean age in case and control mothers was about 30, and the mean education level was about 14 years in both. More SLE mothers had hypertension, asthma, diabetes, and depression, and, as expected, many more were on anti-inflammatory and immunosuppressive medications.

"The effect of maternal SLE on the risk of allergic conditions was not completely explained by variables like maternal history of allergy, preterm birth, or small for gestational age babies, which are well-recognized risk factors for allergic conditions in offspring," Couture and co-authors wrote.

Immunological links between allergy and autoimmune diseases have been proposed, with one 2010 study suggesting that T-helper type 1 cells and T-helper type 2 cells contribute to SLE. And autoreactive immunoglobulin E and the activation of basophils may promote the production of autoantibodies in SLE.

The Montreal study's findings are consistent with a handful of previous small, observational studies such as that of Sasai and colleagues, which reported a higher prevalence of atopic dermatitis and bronchial asthma in the children of SLE mothers (64% and 28%) than in controls (19% and 9%). And a small study by Sanchez-Manubens and associates found a 20.5% asthma rate in newborns of mothers with autoimmune disease.

"In these prior observational studies and in ours, differences in the risk of allergies between SLE offspring and unexposed children could potentially be due to increased reporting by SLE mothers," Couture and associates wrote.

In 2015, the McGill research group reported double the risk of autism in children born to SLE-affected mothers, suggesting that, as with allergies, factors beyond genetics play a role in this disorder.

Study limitations included the uncertainty about case ascertainment inherent in administrative databases. The study could not rule out overestimation of allergic cases of angioedema, urticaria, and allergy without other indication since it was impossible to differentiate etiologies such as viral versus IgE-mediated cases using diagnostic codes.

In addition, the study might have lacked the power to estimate the risk of preterm birth and small for gestational age on allergic outcomes. Furthermore, information on in utero drug exposures was available only for children whose mothers had drug coverage throughout pregnancy – about 20% of the entire cohort, thereby educing the study's power to examine the effect of this variable on the risk of allergic conditions.

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